unconjugated bilirubin is joined with glucoronic acid in the liver, making it conjugated (=soluble)

conjugatde bilirubin passes into the gallbladder and on to the small intestine, where it is converted into urobilinogen and excreted in urine by the kidneys or to stercobilinogen and excreted in faeces

The types of jaundice are:

1. Pre-hepatic = unconjugated

caused by:

haemolysis

lack of UDP: Gilberts, Crigler Najjar

urine/faeces colours normal

2. Hepatic = both conjugated and unconjugated

caused by:

infection: HBV, HCV, EBV

Wilsons

Budd-Chiari

Dubin-Johnson/Rotor syndromes

cirrhosis

drugs:

anti-TB meds

statins

sodium valproate

MAOIs

halothane

paracetamol OD

urine dark, faeces normal

3. Post-hepatic = conjugated = obstructive/cholestatic

gallstones

pancreatic cancer

cholangiocarcinoma

primary bilary sclerosis

sclerosing cholangitis

Mirrizi's syndrome = obstructive jaundice secondary to compression of the common hepatic duct by a gallstone impacted in the cystic duct

Zollinger-Ellison syndrome is a rare condition in which there are multiple gastric and duodenal ulcers in association with gastrin-secreting adenoma.

The adenoma is usually pancreatic in origin but may be found in the stomach or duodenum.

50-60% of the adenomas in Zollinger-Ellison syndrome are malignant.10-30% are associated with MEN-1.
(quick recap: MEN 1 = pancreatic tumours, parathyroid tumours and pituitary tumours)

Presentation:

epigastric pain from the ulcers

diarrhoea

malabsorption/steatorrhoea from inactivation of pancreatic enzymes

Diagnosis is by a raised fasting gastrin level.
Note gastrin levels will also be raised in achlorhydria - this differential can be eliminated by doing a secretin stimulation test which will cause a raised gastrin level in Zollinger-Ellison syndrome but no rise with achlorhydria.

Treatment is with high dose PPI (eg 60mg/day).Ocreotide (somatostatin analogue) may help with symptom relief.

This battle will briefly run through 4 conditions associated with congenital hyperbilinrubinaemia....

1. Gilberts

This is the absolute classic. Gilberts is inherted in an autosomal recessive fashion and affects 1-2% of the population.

Gilberts is due to low levels of UDP glucuronosyltransferase.
It results in a rise in unconjugated bilirubin.

Gilberts is entirely benign and many sufferers only take on a yellow tinge when they have a concurrent illness.

2. Crigler Najjar

There are 2 types of Crigler Najjar - type 1, which is autosomal recessive, and type 2, which is autosomal dominant.

It is due to there being no UDP glucuronosyltransferase
This results in a catastophic rise in unconjugated bilirubin.

Unless the sufferer has a liver transplant they are likely to die as a baby.

3. Dubin Johnson

Dubin Johnson is an autosomal recessive condition in which there is a mutation in the cMOAT transport protein resulting in a defect of hepatic excretion of bilirubin and a rise in conjugated bilirubin.

This manifests as intermittent jaundice with RUQ pain.

Tests to confirm Dubin Johnson include:

coproporphyrin I levels being 3-4x higher than coproporphyrin III- in normal subjects this is reversed

normal levels of urine coproporphyrin but 80% being the I isomer, when normally this would be 25%

at postmortem: liver has black pigmentation

Happily Dubin-Johnson is a benign condition

4. Rotor syndrome

Rotor syndrome is an autosomal recessive disorder which is similar to Dubin-Johnson and is also due to a defective mechanism of excretion of conjugated bilirubin.

It is also benign.

Rotor syndrome can be differentiated from Dubin-Johnson as:

Dubin-Johnson has normal levels of urinary coproporphyrin while Rotor syndrome has high levels

liver in Dubin-Johnson has black pigmentation whereas in Rotor syndrome it is normal

Note that technically a Swan-Ganz catheter/cardiac catherisation is needed to diagnose pulmonary hypertension; however, cardiac echo is often used. Echo reports tend to quote systolic pulmonary artery pressure rather than mean - to convert to mean multiply by 0.61 and add 2.

Cor pulmonale is right heart failure caused by pulmonary hypertension.

Features of pulmonary hypertension

Tends to present with progressive shortness of breath.

On examination look for signs of right heart failure:

right ventricular heave

raised JVP, a waves

loud P2

pansystolic murmur - tricuspid regurgitation

Types of pulmonary hypertension

Primary - accounts for <1% pulmonary hypertension
10% of cases are familial and inherited in an autosomal dominant fashion

Scromboid poisoning is caused by the ingestion of amines, mainly histamines, which are produced by bacterial decarboxylation of histadine in fish meat (mainly tuna, mackeral, sardines, anchoives, marlin)

The commonest cause of scromboid poisoning is ingestion of spoiled fish following improper refridgeration. Cooking well will not inactivate the hisatmines that have been produced.

Degree of symptoms correlates to amount of fish consumed.

Symptoms include:

nausea

abdo pain

diarrhoea

flushing

rash

headache

palpitations

hypo or hypertension

Onset of symptoms tends to be within 10 to 30 mins but may take up to 2 hours
Symptoms tend to settle within 36 hours

The toxin causes a descending flaccid paralysis by binding irreversibly to the presynaptic membranes of the neuromuscular junction, blocking acetylcholine release.

Signs include:

flaccid paralysis

dysarthria

ptosis

fixed/dilated pupils

dry mouth

respiratory arrest

Botulism may be caused by food or by wound infection. Heroin users are at high risk.
All commericial canned food has to undergo a 'botulum cook' at 121C.
Honey can contain botulum and as a result it is not recommended to give honey to infants under 1 yr of age.

The cause is not known although demodex follicularumis hypothesised to be involved as it occurs in larger numbers on suffers of acne rosacea than the general population. Overuse of topical steroids can cause a condition like acne rosacea.

If the condition is mild topical metronidazole is used.
In severer cases oral oxytetracycline is given.

Homocystinuria is an autosomally recessive inherited condition in which there is decreased activity of cystathionine beta synthase resulting in accumulation of homocysteine and methionine which interferes with collagen cross-linkage.

Features include:

Marfanoid body habitus

spontaneous retinal detachment

downwards lens dislocation

osteoporosis

venous and arterial thrombosis

low IQ

Diagnosis is with the cyanide nitroprusside test which detects elevated urinary homocysteine.

Note how similar it looks to erythema ab igne (AKA livedo recticularis e calore) which is a rash caused by prolonged heat exposure, for example by sitting by a radiator or holding a hot water bottle. (photo form wiki commons, taken by Dr Heilman)

lupus anticoagulant - an inhibitor of the coagulation pathway in vitro; pro-coagulant in vivo

anti cardiolipin antibodies - IgG and IgM

Management is with aspirin post thrombus, or if recurrent thromboses despite aspirin warfarin.

In pregnancy expert advice is needed; in general aspirin is taken once pregnant and LMWH started once the fetal heart is seen. This is continued until 34 weeks. This regime results in 70% success compared with 10% with nothing.

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About Me

UK junior doctor attempting to revise for MRCP whilst maintaining her sanity/free time for the things in life doctors know are actually luxuries, like sleeping and eating.
No responsibility taken for any inaccuracies contained within, and please be aware that as this blog will often be written in a sleep/glucose deprived state the potential for whoopsies is great.
If you want to email me with corrections/suggestions/offers of chocolate, please do so to: marietreasure7 (at) gmail.com